Hindawi Publishing Corporation

Epilepsy Research and Treatment

Volume 2012, Article ID 849540, 16 pages
doi:10.1155/2012/849540

Review Article
Temporal Lobe Epilepsy in Children

Katherine C. Nickels,1 Lily C. Wong-Kisiel,1 Brian D. Moseley,2 and Elaine C. Wirrell1

1 Divisions of Epilepsy and Child and Adolescent Neurology, Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
2 Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA

Correspondence should be addressed to Elaine C. Wirrell, wirrell.elaine@mayo.edu

Received 10 June 2011; Accepted 21 August 2011

Academic Editor: Seyed M. Mirsattari

Copyright © 2012 Katherine C. Nickels et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

The temporal lobe is a common focus for epilepsy. Temporal lobe epilepsy in infants and children differs from the relatively homo-
geneous syndrome seen in adults in several important clinical and pathological ways. Seizure semiology varies by age, and the ictal
EEG pattern may be less clear cut than what is seen in adults. Additionally, the occurrence of intractable seizures in the developing
brain may impact neurocognitive function remote from the temporal area. While many children will respond favorably to medical
therapy, those with focal imaging abnormalities including cortical dysplasia, hippocampal sclerosis, or low-grade tumors are likely
to be intractable. Expedient workup and surgical intervention in these medically intractable cases are needed to maximize long-
term developmental outcome.

1. Introduction Harvey et al. identified 63 children with new-onset TLE over

The temporal lobe plays a vital role in epilepsy and is the
most frequent lobe involved in focal onset seizures. Temporal
lobe epilepsy in children and infants has clear clinical fea-
tures which make it distinct from the fairly homogeneous
syndrome seen in adults.
Reported studies of temporal lobe epilepsy (TLE) in chil-
dren are heavily biased towards those with medically in-
tractable epilepsy, and few studies focus on cohorts who are
newly diagnosed. This paper will address pediatric-specific
aspects of TLE, including clinical semiology in young chil-
dren, pediatric epilepsy syndromes involving the temporal
lobe, medical and surgical management, associated psychi-
atric and cognitive disorders, and long-term outcomes.
2. Epidemiology
The overall incidence of new-onset epilepsy in children ran-
ges from 33 to 82 per 100,000 children per year, and approx-
imately half- to two-thirds of these children have focal-onset
seizures [1–6]. However, the exact incidence of TLE is not
known, as the specific lobe of onset is not specified in most
incidence studies. Compared to adults, focal seizures in chil-
dren are more likely to arise from extratemporal foci. Simon
a 4-year period in the state of Victoria, Australia (population
4.4 million) [7]. In our 30-year cohort of new-onset epilepsy
in children, 276/468 (59%) had nonidiopathic focal epilepsy.
Of these, 20 (7.2%) had a focal lesion on MRI in the
temporal region (10: mesial temporal sclerosis, 1: malfor-
mation of cortical development, 2: ischemia/gliosis, 1: tum-
our, and 4: vascular malformation), while 17 (6.1%) had nor-
mal imaging and a single focus of epileptiform discharge in
the temporal region. Therefore, it was determined that TLE
was responsible for 8% of all pediatric epilepsy, and for 13%
of all focal seizures in our cohort [1].
3. Semiology of Temporal Lobe Seizures
in Children
One of the defining characteristics of TLE is its unique semi-
ology. These features, which have been studied extensively
in adults, can help clinicians to localize seizures to the tem-
poral region prior to capturing interictal/ictal epileptiform
discharges. Such information is particularly valuable when
evaluating patients with medically intractable epilepsy. When
concordant with structural magnetic resonance imaging and
electroclinical data, seizure semiology can facilitate the iden-
tification of candidates for successful surgical interventions
2 Epilepsy Research and Treatment

[8]. The semiology of temporal lobe seizures in children has

previously been investigated, although less robustly than in
adults. Like adults, children with TLE are more likely to
demonstrate specific semiologies when their seizures arise
from specific portions of the temporal lobe (e.g., mesial, lat-
eral, or insular). However, in contrast to adults, the semiol-
ogy of TLE in children can be profoundly affected by age and
brain development. Such changing semiology can present a
challenge to physicians attempting to identify (and effectively
treat) children with TLE.

3.1. Semiology of TLE in Infants and Toddlers (Age 0–3

Years). Some of the most difficult temporal lobe seizures to
identify utilizing semiology alone are those arising in infants
and toddlers. Unlike older children, infants and toddlers (a)
are more likely to display seizure semiologies reminiscent
of extratemporal and generalized epilepsies. Previous stud-
ies have documented an inverse relationship between the
occurrences of ictal motor manifestations and age [9–14].
Such motor manifestations include tonic, clonic, myoclonic,
and hypermotor seizures, and epileptic spasms [9, 10, 14].
Despite their unilateral origin, such movements can appear
bilateral and symmetric, complicating attempts to lateralize
seizure onset [9, 13]. They can also be easily mistaken
for frontal lobe seizures [9, 13]. The likely reason for
the increased motor manifestations of TLE in infants and
toddlers is the presence of focal pathology in the setting of
incomplete CNS myelination [14, 15]. This is particularly
pertinent with regards to the limbic system, which is resistant
to synchronization in an immature state [10, 16–19]. The
occurrence of epileptic spasms in young children with tem-
poral lobe pathology is likely secondary to rapid secondary
generalization of focal onset seizures via dysfunctional cor-
tical-subcortical interactions (particularly involving the tha-
lamus, basal ganglia, and other brain stem structures). This
can result in the generalized semiologic and EEG appear-
ances, making identification of the ictal-onset zone problem- (b)
atic (Figure 1) [20, 21].
One of the hallmarks of TLE in adults is the occurrence of Figure 1: This 2-year-old girl had onset of infantile spasms at the
automatisms. Although automatisms can be seen in infants age 6 months, which were refractory to three antiepileptic medica-
tions. During the clusters of spasms, she had head drops, nonforced
and toddlers with TLE, they are typically simpler than those
head turn, and eye deviation to the right, with elevation of both
observed in older children and adults [9, 10, 12, 22– upper extremities. Her EEG (a) shows a generalized sharp wave
25]. These simpler automatisms include oroalimentary (lip followed by high frequency and low-amplitude activity during the
smacking), gestural (hand fumbling), and blinking move- spasm (50 microvolts/mm, 30 mm/sec). Her coronal FLAIR MRI
ments [9, 12, 24, 25]. This difference may arise from the (b) shows a lesion in the right temporal region, which was found to
limited repertoire of voluntary fine motor gestures in young be a ganglioglioma. She has remained seizure-free since surgery.
children. Once such gestures develop later in life, they can
be incorporated into complex automatisms [9, 22]. Given
the lack of well-developed verbal communication skills in seizures [9, 10]. This age group is more likely to demonstrate
children aged 0–3 years, it is usually impossible for clinicians dystonic posturing, versive/nonversive head turning, and
to properly assess for auras at seizure onset [9, 12, 26]. eye/mouth deviation [9, 23, 25, 27]. Dystonic posturing,
Rather, the earliest signs of such seizures in infants and eye/mouth deviation, and versive head turning have been
toddlers may be behavioral arrest, staring, and lip cyanosis found to lateralize to the contralateral hemisphere in this
[25]. population, with correct lateralization in 75–100% of cases
[23]. Nonversive early head turning correctly lateralizes to
3.2. Semiology of TLE in Preschool and Early School-Age Chil- the ipsilateral hemisphere in 80% of cases in this age group
dren (Age 3–6 Years). In contrast to infants and toddlers, [23].
preschool and early school-age children with TLE have In preschool and early school-age children with TLE,
better developed lateralizing motor manifestations with their more complex automatisms can be observed. These include
Epilepsy Research and Treatment
the oroalimentary automatisms seen in younger (age 0–3
years) children in addition to staring, looking around, and/or
hand clapping [9, 10, 23, 25]. However, more complex au-
tomatisms are still less likely to be observed in this age group
versus older children (age >6 years) and adults [23, 25]. They
are also less likely to correctly lateralize to the ipsilateral
hemisphere than in older children (50% versus 100%) [23].
Although children between the ages of 3 and 6 years with
TLE are more likely to note auras at seizure onset than their
younger counterparts, this can still be difficult to assess
(given the subjective nature of such symptoms). Rather than
asking children with presumed TLE about auras, it may be
more prudent for clinicians to ask parents/caregivers about
behaviors associated with such phenomenon. For example, a
child who consistently cries or runs to a parent/caregiver at
seizure onset may be experiencing ictal fear; this frequently
localizes to the mesial temporal region [28, 29]. Conversely,
children who demonstrate stereotyped unilateral ear plug-
ging at the onset of seizures may be experiencing an auditory
aura localizing to the contralateral superior temporal gyrus
[30].
3.3. Semiology of TLE in Older Children and Adolescents (Age
>6 Years). Beyond the age of 6 years, children with TLE dis-
play much of the same seizure semiology as their adult coun-
terparts. Some older children with TLE will report a pro-
drome hours (or potentially even days) prior to seizure onset.
Such prodromes can consist of headaches, irritability, insom-
nia, personality changes, and/or a sense of impending doom
[28]. However, children with TLE are less likely to experience
such prodromes versus those with generalized tonic-clonic
seizures [28]. Auras are common in older children with TLE
(particularly mesial temporal lobe epilepsy) [25]. The most
common aura reported by older children is an epigastric-
rising sensation [28]. Other auras include olfactory, gus-
tatory, somatosensory, auditory, visual, and other visceral
(oropharyngeal, abdominal, genital, and retrosternal) alter-
ations in self-perception and psychic (déjà vu, jamais vu,
and/or a dreamy state) phenomena [28]. Such auras often
yield the most useful information when attempting to lo-
calize seizure onset correctly. Seizures associated with ma-
cropsia, micropsia, macroacusia, or microacusia typically
arise from the lateral temporal region [28]. Olfactory and
gustatory hallucinations characteristically arise from the
uncus [28]. Even emotions such as fear, strangeness, or em-
barrassment can represent simple partial seizures, sometimes
originating from the amygdala [28].
Compared to children age 0–6 years, older children and
adolescents with TLE are more likely to demonstrate au-
tomatisms with their seizures [10, 23]. Such automatisms
include oroalimentary (lip smacking and swallowing) and
gestural symptoms (picking, fumbling, and aimless move-
ments) [28, 31]. When involving a single extremity, automa-
tisms are a reliable lateralizing sign to the ipsilateral hemi-
sphere; one study even reported 100% accuracy in lateraliza-
tion in this age group [23]. Children age >6 years can also dis-
play tonic or dystonic posturing of an extremity (particularly
the arm) with TLE, providing the seizure involves the motor
strip [28]. Such posturing can assist clinicians in correctly
3
lateralizing seizure onset to the contralateral hemisphere [28,
32]. However, care must be taken not to assume temporal
localization with such posturing, as it can also arise from a
seizure focus in the frontal lobe [28].
When seizures arising from the temporal lobe in children
result in loss of consciousness, it is believed that there has
been bilateral limbic involvement [28]. Complex partial sei-
zures of temporal lobe onset can last for several minutes,
which is typically longer than complex partial seizures arising
from extratemporal (e.g., frontal) regions [28]. Such seizures
are also more likely to secondarily generalize than similar
seizures in younger children [10, 23]. Postictally, children
with complex partial seizures of temporal lobe onset can dis-
play confusion, disorientation, fatigue, headaches, and con-
tinued automatisms [28]. Such behaviors can last for minutes
to hours and can be difficult to clearly delineate from ictal
phenomena [28]. However, they tend to be briefer than
similar postictal behaviors demonstrated by adults with new
onset TLE [27].
3.4. Abdominal Epilepsy of Temporal Lobe Onset in Children.
A semiology of TLE which is more common in children ver-
sus adults is abdominal epilepsy. These seizures, which are
typically accompanied by impairment of consciousness, are
accompanied by abdominal pain and emesis [28]. The dis-
comfort is usually periumbilical, colicky, and severe and
can be accompanied by headache, dizziness, syncope, and
temporary loss of vision [28, 33]. The duration of abdominal
pain is usually limited to 10–15 minutes and may be as-
sociated with sweating, stomach growling, salivation, and
flatus [28]. Such a diagnosis can be difficult for clinicians to
make, ultimately requiring prolonged video EEG monitoring
to establish [28].
3.5. Autonomic Effects of Childhood TLE. Another potentially
useful marker of TLE in children is autonomic (cardiac and
respiratory) changes. The most commonly observed auto-
nomic change in temporal lobe seizures in children is ictal
tachycardia. This occurs with roughly equal frequencies in
children versus adults [34] and can be observed in up to
98% of all childhood temporal lobe seizures [35]. This is
particularly true if they are of right hemispheric onset [35].
In contrast, ictal bradycardia is rare in children, occurring in
less than 4% of monitored seizures [36]. Such seizures are
typically extratemporal in onset [35, 36].
One of the most dramatic autonomic disturbances that
can occur during temporal lobe seizures in children is hypox-
emia and/or apnea. Nearly half of all children and one-fourth
of their seizures captured in inpatient monitoring units are
characterized by desaturations <90% [36]. Such desatura-
tions were not trivial, with nearly one-third (32.1%) falling
to <60% [36]. Ictal hypoxemia in children is not specific for
TLE and is more likely to be observed when partial seizures
secondarily generalize [36]. However, in younger children
(age 2–6 years), apneic attacks may be the sole manifestation
of TLE [28, 37]. Such hypoxemia/apnea could theoretically
exacerbate bradycardia induced by carotid chemoreceptors,
causing further respiratory suppression.
4 Epilepsy Research and Treatment
Figure 2: This EEG shows interictal left temporal spikes recorded
from a 13-year-old boy with left temporal lobe epilepsy due to
mesial temporal sclerosis (10 microvolts/mm, 30 mm/sec).
4. EEG Features of TLE
The scalp EEG in patients with TLE is important for making
the initial diagnosis of epilepsy, as well as localizing seizure
onset. The value of scalp EEG is improved by ensuring a sleep
recording during routine EEG. Furthermore, localization of
seizure onset is improved through the use of additional EEG
electrodes, either sphenoidal or inferolateral temporal, as
well as closely placed electrodes [38–41].
4.1. Interictal EEG Features of TLE. The interictal EEG in
TLE is typically characterized by temporal spike or sharp-
wave discharges and temporal intermittent rhythmic delta
activity (TIRDA). Temporal spike or sharp-wave discharges
are highly epileptogenic discharges that are maximal over
the anterior temporal region and may prominently involve
the ear leads (Figure 2). There is often increased activation
of spike and sharp-wave discharges during drowsiness and
sleep, with nearly 90% of patients with temporal lobe seizures
showing spikes during sleep [42]. The spike-wave discharges
may occur independently or synchronously over the bilateral
temporal regions. However, most patients with bitemporal
interictal EEG patterns are found to have unilateral temporal
lobe seizures [39].
TIRDA has also been seen in patients with TLE. Like the
spike and sharp-wave discharges, TIRDA is also most promi-
nent during drowsiness and NREM sleep (Figure 3). It is
characterized by rhythmic trains of low- to moderate-am-
plitude, monomorphic delta frequency slow waves over uni-
lateral or bilateral temporal regions. The monomorphic slow
waves are without clinical correlate and must be differenti-
ated from the polymorphic delta activity that would be seen
with a focal lesion over the temporal region. TIRDA has the
same epileptogenic significance as temporal spike and sharp-
wave discharges [42].
Figure 3: Left temporal intermittent rhythmic delta activity
(TIRDA) in a 12-year-old boy with temporal lobe epilepsy. TIRDA
consists of rhythmic trains of low-moderate amplitude monomor-
phic delta frequency slow waves and is most commonly seen during
drowsiness or sleep (15 microvolts/mm, 30 mm/sec).
4.2. Ictal EEG Features of TLE. The temporal lobe has the
lowest threshold for seizures. However, it is important to
note that scalp ictal and interictal EEG recordings in children
may be poorly localizing, even in TLE, due to incomplete
or abnormal brain maturation. A focal lesion can present
with generalized or multiregional epileptiform discharges in
infants and young children (Figure 1). Similarly, the ictal
EEG in a focal seizure of anterior temporal lobe origin may
initially demonstrate lateralized or generalized scalp EEG
changes [43].
Typically, the scalp EEG during a temporal lobe seizure
will demonstrate moderate- to high-amplitude rhythmic
paroxysmal activity that is maximal over a unilateral tem-
poral region (Figure 4). This may progress to generalized
rhythmic slowing that is maximal on the side of seizure onset
[44]. Prior to seizure onset and postictally, there may be
increased interictal temporal or bitemporal spike wave activ-
ity. Postictally there may also be focal temporal or generalized
arrhythmic slow wave activity. This must be distinguished
from continuing seizure activity.
5. Differential Diagnosis
Temporal lobe seizures and temporal EEG discharges are seen
in several pediatric epilepsy syndromes. Seizures may be due
to structural abnormalities, either congenital or acquired.
Classically, mesial temporal lobe seizures are seen with hip-
pocampal sclerosis, often preceded by a history of prolonged
or atypical febrile seizures. Mesial TLE with hippocampal
sclerosis has been identified as a distinctive constellation in
the most recent epilepsy syndrome classification [45].
However, nonlesional temporal lobe syndromes must
also be recognized, including autosomal dominant lateral
TLE, idiopathic partial epilepsy with auditory features, famil-
ial mesial TLE, and partial reading epilepsy.
Autosomal dominant lateral TLE, also known as auto-
somal dominant partial epilepsy with auditory features,
is associated with mutations in the leucine-rich, glioma-
inactivated 1 (LGI1) gene in approximately 50% of families
Epilepsy Research and Treatment 5

(a)

(b)

Figure 4: (a) shows 3 consecutive pages of EEG illustrating the onset of a left mesial temporal seizure in a 13-year-old girl with a history of
a prolonged febrile convulsion at the age of 18 months (10 microvolts/mm, 15 mm/sec). Her coronal FLAIR MRI (b) shows left mesial
temporal sclerosis. Her seizures were intractable to medical therapy, but she became seizure-free after surgery.

[46, 47]. Median age at onset is in late adolescence (range 1–
60 years), and the focal seizures have prominent elementary
auditory auras. Aphasic seizures are seen in 17% of cases and
secondarily generalized seizures in 90%. Neuroimaging is
usually normal and the clinical course is benign, with most
patients achieving good control with antiepileptic medica-
tions. Epilepsy with similar features can be seen without
family history and without LGI1 mutations [48].
In review of 100 individuals from 20 families, Crompton
et al. characterized the clinical features of familial mesial
TLE, which they propose is inherited in a polygenic (rather
than autosomal dominant) manner [49]. Median age at
6 Epilepsy Research and Treatment
Figure 5: This EEG is from an 8-year-old boy with early morning
seizures consisting of unilateral facial twitching, drooling, and
dysarthria. The EEG during sleep shows bilateral centrotemporal
sharp waves (most prominent on the left) suggestive of benign
childhood epilepsy with centrotemporal spikes (15 microvolts/mm,
30 mm/sec). These “rolandic” spikes most commonly show a dipole
on referential montage, with frontal positivity and temporal nega-
tivity.
seizure onset was 15 years (range 3–46 years), antecedent
febrile seizures were seen in 9.8%, and nearly all patients had
normal neuroimaging. Semiology is characterized by déjà
vu, fear, and nausea, with evolution to a focal seizure with
or without loss of awareness. Most patients had a relatively
benign course with good response to medication.
Partial reading epilepsy presents with ictal alexia pro-
voked by reading. The seizure is accompanied by left tempo-
ral ictal discharge although independent bilateral temporal
seizure onset has been reported [50].
TLE must be differentiated from other pediatric epilepsy
syndromes in which there is significant activation of spike-
wave discharges during sleep. These include Landau Kleffner
syndrome (LKS), continuous spike-wave during slow-wave
sleep syndrome (CSWS), and benign childhood epilepsy with
centrotemporal spikes (BCECTSs). Although epilepsy syn-
dromes such as LKS and CSWS have been proven to be
secondary to focal pathology amenable to resection in select
children [51, 52], this infrequently localizes to the temporal
lobe.
LKS and CSWS are both pediatric epilepsy syndromes
that present during preschool or early school years with
regression of skills with or without seizures. Early in the
presentation, the EEG demonstrates spike and slow-wave dis-
charges maximally over the frontotemporal and centrotem-
poral regions with increased activation during sleep. How-
ever, over time the spike-wave discharges during non-REM
sleep become nearly continuous, with discharges occupying
nearly 85% or more of sleep. The nearly continuous spike-
wave discharge during sleep is termed electrical status ep-
ilepticus in slow-wave sleep (ESES). ESES resolves upon
awakening and is without clinical accompaniment. The elec-
trical status and seizures resolve in later childhood or adoles-
cence in both LKS and CSWS. With resolution, there is some
developmental improvement although development typi-
cally does not normalize in either syndrome [53]. Although
there are clinical and electrophysiologic similarities in LKS
and CSWS, these are clinically distinct syndromes.
LKS presents primarily as language regression and ac-
quired auditory agnosia in children with previously normal
development. This progresses over weeks to months and is
often accompanied by irritability, hyperkinesia, attention
deficit disorder, and autistic-like behavior [54]. Neuroimag-
ing is normal, and the etiology is unknown. Seizures are
common in LKS and may include focal seizures with or
without loss of awareness, generalized tonic-clonic and atyp-
ical absence seizures although the most common seizure is
a nocturnal hemiclonic seizure. The seizures are typically
infrequent and easily treated. The epileptiform discharges
and ESES in LKS occur maximally over the temporal regions,
which correlates with receptive language regression [55–61].
In contrast to LKS, CSWS presents with global regression,
including difficulties with expressive language, temporo-
spatial skills, hyperkinesis, memory deficits, motor deficits,
and poor behavior. Language comprehension is typically
spared. Development prior to regression may be normal or
delayed [56, 62–66]. In addition, radiologic abnormalities
including atrophy and cortical migration abnormalities are
frequently found in CSWS [56, 61, 67–69]. The majority of
children with CSWS present with seizures, including gen-
eralized tonic-clonic, typical, or atypical absence, and focal
seizures with or without loss of awareness. Atonic seizures
can also occur, but tonic seizures do not. The seizures can
occur frequently, up to several times per day [56, 57, 70]. The
epileptiform discharges and ESES in CSWS occur maximally
over the frontal head regions, which correlates with the
global regression, expressive language abnormalities, and
motor impairment seen in these children.
Finally, temporal lobe epilepsy must also be differentiated
from benign childhood epilepsy with centrotemporal spikes
(BCECTS). BCECTS presents in early- to mid-childhood
with infrequent seizures. The seizures are commonly pre-
ceded by paresthesias of the face and hand, followed by
speech arrest and excessive salivation, ipsilateral facial myo-
clonus that spreads to the ipsilateral hand, and hemiclonic or
generalized tonic-clonic seizures. They typically occur out of
sleep [71–73].
Like LKS and CSWS, the EEG in BCECTS demonstrates
dramatic activation of epileptiform discharges during sleep,
although typically occupying less than 85% of the sleep
record. The epileptiform discharges in BCECTS are high am-
plitude, blunt, and maximal over the centrotemporal region
(Figure 5). Serial EEGs may also demonstrate a shifting
asymmetry of the centrotemporal discharges [55, 62, 71].
Children with BCECTS typically have normal cognition,
and the seizures respond well to antiseizure medications.
Furthermore, due to the infrequent nature of the seizures,
medication may not be necessary. The prognosis of BCECTS
is excellent, with spontaneous remission occurring in all chil-
dren during adolescence.
6. Management of TLE in Children
Similar to other focal onset epilepsies, children with tem-
poral lobe epilepsy are often initially treated through med-
ication management. However, temporal lobe epilepsy often
does not respond completely to antiseizure medications
Epilepsy Research and Treatment
(AEDs). Therefore, both medical and surgical treatments will
be discussed.
6.1. Medical Management. The goal of epilepsy management
is long-term seizure freedom with minimal or no unaccept-
able side effects. Despite the availability of new antiepileptic
drugs, there is no single AED that has proven superior effi-
cacy in the management of focal seizures [74]. The choice
of which drug to use depends on the individual patient
characteristics and medication side effect profile. While
newer drugs (e.g., oxcarbazepine, levetiracetam, lamotrigine,
topiramate, etc.) are considered to have improved side effect
profiles compared to older AEDs (phenytoin, phenobarbital,
and carbamazepine), some of the newer medications carry
greater risk for cognitive impairment (topiramate, zon-
isamide) or behavior problems (levetiracetam).
Furthermore, many children continue to have seizures in
spite of adequate AED treatment. If two or more appropriate
AEDs at adequate doses and duration have failed to control
seizures, the probability of seizure freedom is low and di-
minishes progressively with further unsuccessful medication
trials. Among newly diagnosed adults with epilepsy without
prior medication trials, 47% to 50% became seizure-free
with their first AED, 11% with their second drug, and less
than 3% with their third monotherapy or with combination
of two drugs [75, 76]. In children, the response to medi-
cation is more favorable. Carpay et al. found that 51% of
children whose first medication failed for lack of efficacy
had a good response to a second agent [77]. However, the
likelihood of achieving a remission of longer than one year
with subsequent drug regimens was only 29% after two
medications failed, and 10% after three medications failed.
In a separate study by Berg et al., among children whose
seizures persisted despite trials of two AEDs, only 38%
achieved a 1-year remission and 23% achieved a 3-year
remission at last contact [78]. In children with cryptogenic
or symptomatic focal epilepsy, the outcome may be more
concerning; only 29% of children became seizure-free with
a second monotherapy trial [79].
6.2. Surgical Management. Patients with medically refractory
TLE should be evaluated expediently for surgical manage-
ment, given the poor prognosis with additional medication
trials. Hippocampal sclerosis and dual pathology (hip-
pocampal sclerosis and other lesion) were associated with
only 11% and 3% seizure freedom at last followup in medi-
cally treated cases, respectively [80, 81]. Early surgical inter-
vention is also warranted, as long-term AED use carries risks
such as osteopenia and osteoporosis, menstrual irregulari-
ties, sexual dysfunction, reduced fertility, cardiovascular ill-
ness, and drug-drug interactions. Furthermore, children un-
dergoing temporal lobectomy for intractable epilepsy show
improvement in visual memory and attentional functions
[82] and quality of life, with complication rates less than 5%
[83]. However, successful surgery for epilepsy is dependent
upon correctly identifying the ictal-onset zone. Therefore,
careful presurgical evaluation is necessary.
7
6.2.1. Presurgical Evaluations
Prolonged Video EEG. Ictal scalp EEG monitoring is essential
for determining region of seizure onset, especially differen-
tiating mesial versus neocortical onset. This is important for
seizure localization as well as having prognostic implications.
Patients with mesial TLE may have higher seizure-free out-
comes with surgery compared to patients with neocortical
temporal and extratemporal lobe epilepsies, particularly if a
single MRI lesion is present [84].
Although patients with TLE can have seizures without
scalp-recorded ictal EEG patterns, due to insufficient source
area (<10 cm2 ) and lack of synchrony to be detected as ictal
activation, this is uncommon [85]. There are several EEG
differences that can be identified between mesial- and
neocortical-onset temporal seizures.
Distinguishing EEG features of lateral neocortical-onset
temporal lobe seizures include a transitional sharp wave [86],
as well as irregular ≤5 Hz, or repetitive epileptiform activities
at ictal onset [87]. Using simultaneously scalp and intracra-
nial recordings among patients with TLE, intermittent rhyth-
mic delta slowing was highly correlated with the irritative and
seizure-onset zones in patients with neocortical temporal
epilepsy but poorly correlated with the irritative seizure-
onset zone in patients with mesial TLE. The presence of inter-
mittent rhythmic delta slowing among patients with mesial
TLE likely represents epileptogenic propagation involving
the temporal neocortex [88].
Imaging Modalities. Neuroimaging is also important for pre-
surgical evaluation, as patients with lesional TLE, such as
hippocampal sclerosis or foreign tissue lesions (tumor, vas-
cular anomaly), have a higher probability of seizure freedom
after resection than those with normal MRI [89]. Postsurgi-
cal seizure-free outcome is seen in 70% to 90% patients with
mesial TLE with hippocampal sclerosis compared to lowered
seizure-free outcome of 60% in patients with nonlesional
TLE [84].
MRI of the brain with seizure protocol includes images
oriented in the oblique coronal plane, perpendicular to the
long axis of the hippocampal structures [90]. Hippocampal
atrophy and T2 signal abnormality seen on fluid-attenuated
inversion recovery sequences are suggestive of mesial tempo-
ral sclerosis (Figure 4(b)). However, T2 hyperintensity alone
in the hippocampus should not be assumed to be the epilep-
togenic zone because up to 47.5% of healthy volunteers with-
out epilepsy have unilateral or bilateral hippocampal T2
hyperintensity [91]. Quantitative volumetric studies can be
helpful in assessing the hippocampal atrophy, particularly
when there is a question of bilateral atrophy or hippocampal
malrotation [92].
In addition to MRI, multimodality noninvasive imaging
techniques are increasingly used to determine the presumed
epileptogenic focus when the scalp EEG and MRI are non-
localizing or normal. These include subtraction ictal SPECT
coregistered to MRI (SISCOM), positron emission tomogra-
phy (PET), magnetoencephalography (MEG), and magnetic
resonance spectroscopy (MRS).
8 Epilepsy Research and Treatment
SISCOM is a noninvasive modality to determine the
epileptogenic lesion. Intensity differences more than two
standard deviations between interictal and ictal images are
coregistered onto the individual patient’s MRI [93]. This
technique produces semiquantitative maps of cerebral perfu-
sion differences between ictal and interictal states and places
that information in the context of the patient’s own anatomy.
The ability of SISCOM to detect epileptogenic lesions is 88%
as compared to 39% by ictal SPECT alone [94]. Bell et al.
demonstrated that SISCOM abnormality localized to the re-
section site is predictive of seizure-free outcome among
patients with MRI negative TLE [84].
PET is a measure of glucose metabolism using 18 fluoro-
deoxyglucose. During the interictal state, glucose hypome-
tabolism or reduced glucose uptake is present in the epilepto-
genic zone. In patients with TLE and normal MRI, unilateral
PET hypometabolism has a positive predictive value between
70 and 80% [95]. However, it provided no additional infor-
mation for patients with localizing ictal scalp EEG findings
and concordant MRI.
Among patients with mesial TLE, magnetoencephalo-
gram (MEG) may provide additional localizing information
in up to 50% to 60% of patients with nonlocalizing ictal scalp
EEG [96, 97]. On proton magnetic resonance spectroscopy
(MRS), decreased N-acetyl aspartate over creatine ratios is
seen ipsilateral to spikes in patients with TLE with or without
an MRI-evident lesion [98–100]. Similarly, in children with
intractable TLE, decreased N-acetyl aspartate over choline
plus creatine ratio is correctly lateralized to the side of seizure
focus in 55% of cases [101].
Testings for Language and Verbal Memory Lateralization.
Determination of the dominant hemisphere involved in lan-
guage and verbal memory is important for presurgical coun-
seling regarding the potential surgical risks. This is typi-
cally done through a combination of neuropsychological
assessment, intracarotid sodium amobarbital testing, and
functional MRI. Neuropsychological assessment prior to pe-
diatric epilepsy surgery includes age-appropriate, standard-
ized tests to evaluate multiple domains: intelligence, lan-
guage, memory, attention, problem-solving/executive func-
tion, visuospatial and perceptual analysis and reasoning,
academic skills, motor and sensory function, behavior, per-
sonality, emotional status, and adaptive functioning [102].
Such testing identifies areas of existing dysfunction, assists in
determining language lateralization, and provides guidance
in weighing the risks and benefits of surgery.
While Camfield et al. did not find a specific pattern of
impairment in children [103], other studies have noted a
similar pattern of memory deficits to what is seen in adults.
In 22 right-handed children with intractable TLE, verbal
memory dysfunction was worst among children with left
foci compared to those with right foci and controls, whereas
nonverbal dysfunction was most prominent among children
with right foci [102].
In a large study from Germany, pediatric TLE was shown
to have long-lasting impact on verbal learning and memory.
Compared to controls, children and teens with epilepsy failed
to build up an adequate learning and memory performance
in their early years, hit their learning peak at a younger age,
and reached poor performance levels at a younger age [104].
Furthermore, atypical language lateralization is seen among
12% of epilepsy patients, particularly among those with con-
genital lesions or left hemispheric insult before the age of 6
years [51, 105].
Intracarotid sodium amobarbital testing (Wada test) is
used to determine language lateralization and to screen for
verbal memory dominance. Among children who underwent
temporal lobectomy, better verbal memory performance
after injection ipsilateral to the side of surgery than after con-
tralateral injection (Wada memory asymmetries) predicted
preserved postoperative verbal memory capacity [106]. The
difficulty of Wada testing in children is cooperation. How-
ever, Szabo and Wyllie found that using pretest teaching,
emotional preparation, and simplified test items, up to 96%
of children, including those with borderline intelligence and
moderate mental retardation, could complete at least one
injection [107]. Those at greater risk of poor cooperation
included children with full-scale IQ <80, age <10 years, and
seizures arising from the dominant left hemisphere.
Functional MRI (fMRI) is a noninvasive option to deter-
mine language lateralization as well as identify patients at
higher risk of verbal memory decline following surgery [108,
109]. In children, the preoperative neuropsychologic testing
may identify those who can successfully comply and partici-
pate in the functional mapping procedures. If neither Wada
nor fMRI is feasible, language lateralization and verbal mem-
ory capacity may be determined by neuropsychologic testing.
6.2.2. Surgical Techniques. Once the presurgical evaluation is
completed, surgical options are discussed. Classically, resec-
tion has been offered. However, less invasive, nonresective
surgical techniques are potential treatment options, but need
further study.
Resective Surgery. There are two resective surgical options for
mesial TLE. The first is standard anterior temporal resection
or “anterior temporal lobectomy.” The resection line extends
4 to 5 cm from the temporal pole in the nondominant hemi-
sphere and 3.5 cm to 4 cm in the dominant hemisphere. Stan-
dard anterior temporal lobectomy is preferred when seizure
onset occurs in the lateral temporal or neocortical regions.
The second option is selective amygdalohippocampectomy,
which is selective removal of the mesial temporal structures.
One of the primary goals of selective amygdalohippocam-
pectomy is to preserve neuropsychological outcome, but the
evidence for this is equivocal, especially in children. Seizure
outcome following selective amygdalohippocampectomy is
poorer in children than adults, with seizure-free outcome
reported in only 33% of children versus 71% of adults, likely
due to a greater frequency of pathology outside the hip-
pocampus in younger patients [110]. Furthermore, rates of
verbal memory deterioration after left-sided operations have
been shown to be low [111].
Lastly, in patients with a presumed epileptogenic lesion
in the lateral temporal region, lesionectomy with or without
additional hippocampectomy may be performed.
Epilepsy Research and Treatment
To aid in determination of the optimal resective proce-
dure, intraoperative electrocorticography (ECoG) has been
used to localize the irritative zone and guide extent of surgical
resection. ECoG is unlikely to influence surgical resection
in standard anterior temporal lobectomy in patients with
mesial TLE with mesial temporal sclerosis. Among consecu-
tive patients with mesial TLE who underwent standard ante-
rior temporal lobectomy, 72% were seizure-free despite pre-
resection ECoG showing active interictal discharges outside
the area of planned resection in 48% [112]. In tailored tem-
poral lobectomies, intraoperative hippocampal ECoG may
guide the posterior extent of hippocampal resection. In 140
consecutive patients undergoing this procedure, McKhann et
al. showed that removal of all ECoG confirmed epileptogenic
hippocampal tissue, but not the size of resection, correlated
with seizure-free outcome [113].
Although ECoG may be important in children with dual
pathology to ensure complete resection of regions of cortical
dysplasia, the intraoperative setting is limited by sampling
time. ECoG epileptiform activities are exclusively interictal
spikes, as seizures are rarely recorded. Success of epilepsy
surgery depends on the resection of the ictal onset zone
rather than resection of more restrictive irritative zone sug-
gested by interictal spiking [114].
Complications of dominant temporal lobectomy include
language and memory impairments, with naming and flu-
ency deficits seen in 50% [115]. Verbal memory impairment
depends on whether resection was done in the dominant
hemisphere as well as preoperative level of function—those
with higher preoperative function are more likely to show
decline. Transient diplopia due to trochlear nerve palsy can
occur in 1.5% of cases. Significant contralateral visual field
deficits (such as those greater than 90 degrees requiring sus-
pension of driver’s license) are seen in about 35% of patients
undergoing anterior temporal lobectomy, but approximately
38% of these patients experience improvement within the
first year after surgery [116].
Failure of surgical intervention is a disappointment and
challenge for the epilepsy treatment team. Seizure recurrence
typically occurs within the first year of surgery [117]. Evalu-
ations for additional surgical resection should be considered.
Rarely, the presumed postresection seizures are actually
nonepileptic in nature. Video EEG recording and clinical
semiology may identify a small percentage of patients with
nonepileptic seizures.
Nonresective Epilepsy Surgery. Ablative surgery including
radiofrequency and thermal ablation is currently under in-
vestigation. Seizure remission is delayed up to 9–12 months
after stereotactic radiosurgery for mesial temporal lobe ep-
ilepsy, occurring around the time of vasogenic edema on
MRI [118, 119]. The risks and benefits of this procedure
compared to conventional surgery remain to be determined.
Intermittent stimulation of the vagus nerve using a vagal
nerve stimulator is typically reserved for patients who are not
amenable to or have failed to respond to resective surgery.
Additional studies of the potential efficacy of deep brain
stimulation or focal stimulation have been done in adults.
Limited studies on deep brain stimulation of thalamic nu-
9
clei and hippocampi have demonstrated reduced seizure
burden among adult patients [120, 121]. In the prospec-
tive, randomized, double-blind, parallel group stimulation
of anterior nucleus of thalamus trial, sixty percent of the
patient population had TLE. Subjects with seizure origin in
one or both temporal regions had a median seizure reduction
compared to baseline of 44.2% in the stimulated group ver-
sus a 21.8% reduction in subjects receiving control treatment
[122]. For those patients with focal seizure onset that occurs
in nonresectable cortex, a responsive neurostimulator, which
uses seizure detection algorithms to trigger focal stimulation,
is currently being studied in adults, but not yet in children
[123].
7. Pathology
In many children with new-onset TLE, the etiology remains
unknown despite careful neuroimaging. In a community-
based cohort of 63 children with new-onset TLE, children fell
into three etiological groups [7]. Group 1, which accounted
for 16% of cases, had neuroimaging evidence of malfor-
mations or long-standing, nonprogressive tumors. Group 2,
which accounted for 29% of the cohort, had hippocampal
sclerosis or a history of a significant antecedent event, such
as focal or prolonged febrile seizure or intracranial infection.
Finally, the third group, which accounted for the majority
(54%) of cases, had normal neuroimaging and no significant
past history. This group was termed cryptogenic.
In surgical series, there are two features that distinguish
TLE in children from that of adults. Firstly, the prevalence of
hippocampal sclerosis is significantly lower [124]. While this
is the sole pathological feature found in two-thirds of sur-
gically treated adult cases, in pediatric series, tumors and
malformations of cortical development are more common.
Secondly, in children, if hippocampal sclerosis is present,
it is frequently associated with extrahippocampal pathology
such as cortical dysplasia or low-grade tumors. Such dual
pathology has been reported between 31 and 79% of all
cases of mesial temporal sclerosis in children [15, 124–126].
Several possible mechanisms could explain this dual pathol-
ogy. Firstly, factors resulting in cortical dysplasia may also
interfere with the development of the hippocampus and its
connections. Several authors have reported on the existence
of amygdalohippocampal neuronal dysplasia in such chil-
dren, using the term “dysgenetic mesial temporal sclerosis”
[15, 127]. Alternatively, the extrahippocampal lesion could,
in itself, predispose the hippocampal neurons to seizure-in-
duced neuronal loss.
Several recent studies have reported on hippocampal
malrotation (HIMAL) in a proportion of children with ep-
ilepsy [128, 129]. HIMAL results from failure of inversion
of the hippocampus within the medial temporal lobe which
occurs normally in fetal development and appears to be a
rare finding in patients without seizures [130]. Lewis et al.
reported a higher frequency of this finding in children with
prolonged febrile seizures, indicating that it may play a role
in temporal lobe epileptogenesis [129]. However, no study
has focused exclusively on this finding in a cohort of children
with TLE.
10
The association between prolonged febrile seizures, acute
injury to the hippocampus with resultant hippocampal scle-
rosis, and intractable temporal lobe epilepsy remains con-
troversial [131], and the frequency of this association is cur-
rently being investigated by the ongoing FEBSTAT study.
8. Outcomes
8.1. Seizure Outcome. Long-term seizure outcome in TLE is
primarily affected by the underlying etiology. Harvey found
that over half of children in his new-onset cohort were cryp-
togenic [7]. In a recently published population-based, long-
term follow-up study of outcomes in nonidiopathic focal
epilepsy of childhood, those with a cryptogenic etiology fared
much more favorably than the symptomatic group, with
lower rates of intractable epilepsy (7% versus 40%, P <
0.001), higher rates of seizure freedom (81% versus 55%, P
< 0.001), and higher rates of medication freedom in those
who were seizure-free at final followup (68% versus 46%, P =
0.01) [131]. However, some of these cryptogenic cases likely
had a form of familial TLE.
Children with neuroimaging abnormalities including
low-grade tumors, cortical dysplasia, or mesial temporal
sclerosis have a significantly higher likelihood of medical
intractability and should be considered early for resective
surgery. A recent paper summarized outcomes in children
undergoing temporal lobectomy reporting seizure-free rates
of 58–78% with mesial temporal sclerosis, and in 60–91%
of neocortical temporal resections [132]. Children with dual
pathology do not appear to have a poorer prognosis than
those with mesial temporal sclerosis alone, providing both
the hippocampus and the additional epileptogenic lesion are
resected. Failure to resect the second lesion may explain part
of the surgical failure rate following surgery for pediatric
mesial temporal sclerosis, and as such, selective amygdalo-
hippocampectomy is likely to be less successful in children
[110]. Lack of an obvious imaging abnormality or presence
of diffuse pathology is predictive of higher rates of recurrence
[89].
Following surgery, the steepest decline in the proportion
of patients who remain seizure-free is seen in the first post-
operative year. However, several long-term studies have iden-
tified a risk of late relapse [133, 134]. Jarrar et al. reported
that 40% of subjects who were seizure-free at 5 years had
recurrence of seizures at the 15-year-follow-up point [133].
8.2. Cognition and Memory. In adults with TLE, cognitive
concerns are common, with left-sided foci being associated
with deficits in verbal memory and right-sided foci with
visual memory problems. However, when chronic TLE be-
gins in childhood, the impact on cognition appears much
more significant [135]. In a study which compared neu-
ropsychological testing and quantitative MRI volumetrics
in patients with childhood onset chronic TLE, adult onset
chronic TLE, and healthy controls, Hermann et al. found the
most significant neuropsychological abnormalities in the
childhood onset group. Furthermore, in that group, cog-
nitive compromise was widespread and not just limited
to memory function, and MRI studies showed significant
Epilepsy Research and Treatment
reductions in volumetric measurements of total cerebrum
tissue and total white-matter volumes, consistent with the
generalized nature of the cognitive deficits. These findings
suggested that early-onset temporal lobe seizures and their
treatment and/or factors leading to their development have
significant impact on brain regions distant from the region
of primary epileptogenesis.
A recent review of neuropsychological outcomes after ep-
ilepsy surgery, predominantly based on adult studies, showed
specific cognitive changes, such as risk to verbal memory
with left-sided surgery but noted that cognitive improve-
ments may also be seen in some patients [136]. Most studies
in children suggest greater functional recovery following
temporal lobectomy than is seen in adults [82, 137]. In a
multicenter study of 82 children less than 17 years at time
of surgery, children undergoing left temporal lobectomy
overall demonstrated no significant loss in verbal intellectual
functioning and significant improvements in nonverbal in-
tellectual functioning. Those undergoing right temporal
lobectomy had no overall change in intellectual functioning
[138]. However, analysis of individual changes showed that
significant changes were seen in verbal functioning in 19% of
cases (10% declined, 9% improved), and in nonverbal func-
tioning in 18% (2% declined, 16% improved). Predictors of
significant decline included older age at the time of surgery
and structural lesions other than mesial temporal sclerosis.
In most other studies, factors predictive of postoperative
decline in verbal memory include left-sided surgery and
higher baseline verbal IQ [137, 139, 140].
Historically, many studies in children have been limited
by a relatively short postoperative followup and/or low
patient number. Skirrow et al. recently reported on long-
term followup of 42 children undergoing temporal lobec-
tomy for intractable epilepsy and compared them to non-
surgical controls [141]. Children were followed for a mean
of 9 postoperative years; 86% were seizure-free and 57% off
antiepileptic medication. The mean full-scale IQ improved
significantly in surgical patients but remained relatively
unchanged in controls, with a gain of ten or more IQ points
seen in 41% of surgical patients. However, this increase in IQ
was only seen after a follow-up period of 6 years or longer
and was associated with cessation of antiepileptic drugs and
increased brain grey matter volume on MRI. Those with
lower IQs showed the most significant improvement. This
study highlights that surgery for intractable TLE in children
results in favorable cognitive outcome, but that a prolonged
period may be required for this recovery and subsequent
development.
8.3. Psychiatric Conditions. Children with epilepsy are
known to be at higher risk of comorbid psychiatric disorders
[142–144], and those with intractable focal seizures may be
most vulnerable. In a cohort of children with complex partial
seizures, Ott et al. demonstrated psychopathology in 52%,
and those with lower IQ were at higher risk [145].
McLellan et al. assessed the rate and nature of psychiatric
disorders in a cohort of children undergoing temporal lobec-
tomy and then reevaluated this cohort postoperatively. One
or more psychiatric disorders were found in 72% of children
Epilepsy Research and Treatment
preoperatively, but also in an equivalent number postop-
eratively. Only 16% of children had resolution of their
mental health problems after surgery; however, 12% without
a preoperative psychiatric diagnosis developed mental health
problems after temporal lobectomy [146]. The most com-
mon preoperative diagnoses were pervasive developmental
delay (38%), ADHD (23%), oppositional defiant disorder
(23%), and disruptive behavior disorder, not otherwise spec-
ified (42%). While pervasive developmental delay was more
common with younger age at seizure onset and a right tem-
poral focus, no other biological predictors were found for
any other psychiatric conditions. Surprisingly, this study
found no clear relationship between seizure freedom post-
operatively and psychopathology. However, other studies
have shown reduction in behavior and psychiatric problems
following epilepsy surgery in children [147, 148], and further
work focusing on children undergoing temporal lobectomy
is needed.
Mizrahi et al. assessed whether a delay in surgery im-
pacted psychosocial functioning in children with temporal
lobe epilepsy [149]. Higher rates of psychosocial, behavioral,
and educational difficulties in those undergoing later versus
earlier surgery were found, suggesting that early surgery may
ameliorate some of these difficulties.
9. Conclusion
Although TLE is less common in children than adults, it still
comprises a significant portion of pediatric epilepsy. Seizures
arising from the temporal lobe can be difficult to identify
based on semiology alone, particularly in younger children.
Up to the age of 6 years, the traditional semiologic hallmarks
of TLE in adults (including auras, automatisms, posturing,
and head version) are less likely to be observed. Correct
diagnosis often necessitates routine or prolonged EEG re-
cordings. Although the interictal EEG hallmarks of TLE
(including temporal spike or sharp-wave discharges and
TIRDA) are classically seen in older children, young children
may present with generalized or multiregional epileptiform
discharges, further complicating diagnosis. Once identified,
additional workup is warranted to determine if childhood
TLE is lesional (classically low-grade tumors, cortical dyspla-
sia, or mesial temporal sclerosis) or nonlesional (including
autosomal dominant lateral TLE, idiopathic partial epilepsy
with auditory features, familial mesial TLE, and partial read-
ing epilepsy). Care must be taken to differentiate TLE from
other conditions in which there is significant activation of
spike-wave discharges during sleep, including LKS, CSWS,
and BCECTS.
While the majority of children with TLE will achieve sei-
zure freedom with AEDs alone, a significant minority will
prove medically intractable. This is especially true when sei-
zures are symptomatic of an underlying lesion. For children
with TLE who fail two or more AEDs because of lack
of efficacy, expedited epilepsy surgery evaluations are war-
ranted. In addition to prolonged video EEG and MRI,
SISCOM, PET, and MEG can be successfully utilized in this
population to identify appropriate surgical candidates. Given
the greater likelihood of pathology outside the hippocampus
11
in younger patients (including low grade tumors and cortical
dysplasia), standard temporal lobectomy (versus selective
amygdalohippocampectomy) may portend better outcome.
Such intervention can be associated with seizure-free rates
as high as 58–91% and improved neuropsychological out-
comes. Given the significant morbidity associated with un-
controlled childhood TLE, further research into the efficacy
of other interventions (such as radiofrequency/thermal abla-
tion, stimulation of the anterior nucleus of thalamus, and re-
sponsive neurostimulation) is warranted.
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